Feasibility of screening for FA deficiency across different tumor types, defined as adequate number of patients deficient on this pathway [ Time Frame: Up to 12 weeks post-treatment ] [ Designated as safety issue: No ]

Selection of a dose schedule of the combination of mitomycin C and veliparib for phase II trials [ Time Frame: Up to 12 weeks post-treatment ] [ Designated as safety issue: Yes ]

Feasibility of screening for Fanconi anemia (FA) deficiency across different tumor types, and that patients deficient in this pathway (no FancD2 foci formation in their tumors) exist in adequate number to justify further trials [ Designated as safety issue: No ]

Foci produced by the histone variant γH2AX [ Designated as safety issue: No ]

Tumor shrinkage as assessed by radiology [ Designated as safety issue: No ]

Current Other Outcome Measures ICMJE

Not Provided

Original Other Outcome Measures ICMJE

Not Provided

Descriptive Information

Brief Title ICMJE

Veliparib With or Without Mitomycin C in Treating Patients With Metastatic, Unresectable, or Recurrent Solid Tumors

Official Title ICMJE

ABT-888 as Monotherapy and in Combination With Mitomycin C in Patients With Solid Tumors With Deficiency in Homologous Recombination Repair

Brief Summary

This phase I trial studies the side effects and best dose of veliparib when given with or without mitomycin C in treating patients with solid tumors that have spread to other places in the body, cannot be removed by surgery or have come back. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as mitomycin C, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving veliparib together with mitomycin C may kill more tumor cells.

Detailed Description

PRIMARY OBJECTIVES:

I. To screen cancer patients across different histological sites to identify those with functional defects in the Fanconi anemia (FA) pathway in their tumors.

II. To evaluate in PBMC samples for foci produced by the histone variant gamma-H2A histone family, member X (H2AX) in patients receiving mitomycin C with or without ABT-888 in order to assess any possible effect of ABT-888 in the cellular sensing and processing of mitomycin C-induced deoxyribonucleic acid (DNA) double strand breaks.

III. Quantify the number of patients with antitumor responses.

OUTLINE: This is a dose-escalation study of veliparib. Patients are assigned to 1 of 2 treatment arms.

ARM II: Patients receive veliparib PO BID on days 1-7, 1-14, or 1-21. Patients also receive mitomycin C intravenously (IV) over 10-20 minutes on day 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 12 weeks.

Patients receive veliparib PO BID on days 1-7, 1-14, or 1-21. Patients also receive mitomycin C IV over 10-20 minutes on day 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Interventions:

Other: Laboratory Biomarker Analysis

Drug: Mitomycin

Drug: Veliparib

Publications *

Not Provided

* Includes publications given by the data provider as well as publications
identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ICMJE

Completed

Enrollment ICMJE

20

Completion Date

Not Provided

Primary Completion Date

May 2016 (final data collection date for primary outcome measure)

Eligibility Criteria ICMJE

Inclusion Criteria:

Patients must have a histologically confirmed solid malignancy that is metastatic, or unresectable, or recurrent, for which no curative or standard of care exist, or this standard of care is no longer effective

Tumors have been shown to be deficient for the FA pathway, based on Fanconi anemia triple stain immunofluorescence (FATSI) screening

Patients will be consented to have their existing, or about to be obtained, paraffin embedded tumor tissue screened for FA deficiency; screening will be performed on an ongoing basis on the breast, thoracic, gastrointestinal (GI), Georgetown University (GU), and gynecologic (GYN) Ohio State University (OSU) clinics, anteceding and concurrently with the clinical trial; it will continue until the numbers of patients required for the clinical trial are identified and enrolled; based on the estimation from our preliminary data of 15 to 30% of patients, depending on the primary organ site, having tumors deficient for the FA pathway we will need to screen around 300 patients' samples to identify 40-50 patients; none of the eligibility criteria defined above or below will need to be met for the screening portion, since FA deficient patients identified by screening may meet eligibility criteria for the clinical trial at a later time; (e.g., patient is undergoing standard of care treatment at the time of the screening); separate written consents for screening and for the clinical trial will be obtained from patients

Up to two chemotherapy regimens for metastatic disease are allowed; in addition, prior adjuvant/neo-adjuvant chemotherapy, hormonal therapy, molecular targeted therapy or estrogen receptor B (Erb) inhibitor treatments (e.g., erlotinib, Herceptin, sorafenib, sunitinib) will be allowed and will not count towards eligibility; at least 4 weeks must elapse since prior chemotherapy or radiation therapy (two weeks for erlotinib, hormonal therapy, or limited field palliative radiation to bone, brain, or radiosurgery), 6 weeks if the last regimen included nitrosoureas or mitomycin C; previous use of mitomycin C would be restricted to topical applications (bladder cancer) or chemoembolization (e.g., liver tumors)

Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately

Ability to understand and the willingness to sign a written informed consent document

Consent to a baseline (prior to treatment) tumor biopsy and for a repeat biopsy at the time of progression on the event that an antitumor response is demonstrated on the MMC-ABT-888 regimen

Same eligibility as above, except that they will have no limitations related prior number of chemotherapy regimens given; patients could have received prior treatment with PARP inhibitors if used as single agent

Exclusion Criteria:

Patients may not be receiving any other investigational agents

Patients with known central nervous system (CNS) metastases (unless previously resected or irradiated and not clinically active); patients with CNS metastases must be stable after therapy for > 3 months and off steroid treatment prior to study enrollment

History of allergic reactions attributed to compounds of similar chemical or biologic composition as ABT-888 or Mitomycin C